Even in recent years, a Mycobacterium tuberculosis-infected disease (hereinafter referred to as tuberculosis) is one of extremely serious diseases in the world. The progress of the treatment of tuberculosis was started with the discovery of streptomycin (SM), and then antituberculous action of p-aminosalicylic acid (PAS), isoniazid (INH) and rifampicin (RFP) was found. By combined use thereof, most of tuberculosis became treatable and therefore, advanced countries succeeded in rapid decrease of tuberculosis from 1950s. However, lately, with the prevalence of HIV infection, tuberculosis has rapidly increased in Africa and Southeast Asia, and the spread of multidrug resistant tuberculosis has been reported in Japan and USA. In addition, patients of infectious diseases caused by a typical acid-fast bacteria, especially Mycobacterium avium-intracellulare complex (M. avium-intracellulare complex: MAC) tend to increase year by year.
Chemotherapeutic agents currently used for tuberculosis or a typical acid-fast bacterial diseases include RFP, INH, SM, PAS, ethambutol (EB), kanamycin (KM), ethionamide (ETH), pyrazinamide (PZA), enviomycin (EVM), capreomycin (CPRM), cycloserine (CS), prothionamide (PTH), viomycin (VM), and the like, and these pharmaceutical agents are generally used at polypharmacy.
However, they exhibit unsatisfactory effectiveness and safety, for example, insufficient antibacterial activity against multidrug resistant Mycobacterium tuberculosis and toxicity toward lever, kidney, etc.
Under such circumstances, there is anxiety that pathology of these infectious diseases becomes complex and intractable, and therefore, it is strongly desired to promptly develop an effective therapeutic agent which is excellent in antibacterial activity and exhibits no cross resistance.
An object of the invention is to provide a pyridonecarboxylic acid which shows excellent antibacterial activity against Mycobacterium tuberculosis and a typical acid-fast bacteria and exhibits good pharmacokinetics and safety.
Prior patent applications, which is directed to pyridonecarboxylic acid-type synthetic antibacterial agents, all describe pharmaceutical agents against so-called general bacteria such as Gram-negative and Gram-positive bacteria but they describe no action against acid-fast bacteria.